Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38483

or expanding exemptions might

adversely impact small entities and

concluded, as a generic matter, that

there is no adverse economic impact.

The factual basis for the Agency’s

generic certification for tolerance

actions published on May 4, 1981 (46

FR 24950), and was provided to the

Chief Counsel for Advocacy of the Small

Business Administration.

IV. Submission to Congress and the

General Accounting Office

Under 5 U.S.C. 801(a)(1)(A), as added

by the Small Business Regulatory

Enforcement Fairness Act of 1996, EPA

submitted a report containing this rule

and other required information to the

U.S. Senate, the U.S. House of

Representatives, and the Comptroller

General of the General Accounting

Office prior to publication of this rule in

today’s Federal Register. This is not a

‘‘major rule’’ as defined by 5 U.S.C.

804(2).

List of Subjects in 40 CFR Part 180

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: June 30, 1998.

Peter Caulkins,

Acting Director, Registration Division, Office

of Pesticide Programs.

Therefore, 40 CFR chapter I is

amended as follows:

PART 180— [AMENDED]

1. The authority citation for part 180

continues to read as follows:

Authority: 21 U.S.C. 346a and 371.

§ 180.443 [Amended]

2. In § 180.443, by amending

paragraph (b) in the table, for the

commodities ‘‘Peppermint’’ and

‘‘Spearmint’’ by changing the date ‘‘July

1, 1998’’ to read ‘‘1/31/00’’.

[FR Doc. 98–18988 Filed 7–16–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[OPP–300612; FRL–5768–3]

RIN 2070–AB78

Fipronil; Pesticide Tolerance

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes

new tolerances for combined residues of

fipronil, its metabolites MB46136 and

MB45950, and its photodegradate

MB46513, in or on rice grain and rice

straw. In pesticide petition (PP) 7F4832,

Rhone Poulenc AG, Inc. requested these

tolerances under the Federal Food, Drug

and Cosmetic Act (FFDCA), as amended

by the Food Quality Protection Act of

1966 (FQPA).

DATES: This regulation is effective July

17, 1998. Objections and requests for

hearings must be received by EPA on or

before September 15, 1998.

ADDRESSES: Written objections and

hearing requests, identified by the

docket control number, OPP–300612,

must be submitted to: Hearing Clerk

(1900), Environmental Protection

Agency, Rm. M3708, 401 M St., SW.,

Washington, DC 20460. Fees

accompanying objections and hearing

requests shall be labeled ‘‘Tolerance

Petition Fees’’ and forwarded to: EPA

Headquarters Accounting Operations

Branch, OPP (Tolerance Fees), P.O. Box

360277M, Pittsburgh, PA 15251. A copy

of any objections and hearing requests

filed with the Hearing Clerk identified

by the docket control number, OPP–

300612, must also be submitted to:

Public Information and Records

Integrity Branch, Information Resources

and Services Division (7502C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

a copy of objections and hearing

requests to Rm. 119, Crystal Mall #2,

1921 Jefferson Davis Hwy., Arlington,

VA.

A copy of objections and hearing

requests filed with the Hearing Clerk

may also be submitted electronically by

sending electronic mail (e-mail) to: oppdocket@epa.gov. Copies of objections

and hearing requests must be submitted

as an ASCII file avoiding the use of

special characters and any form of

encryption. Copies of objections and

hearing requests will also be accepted

on disks in WordPerfect 5.1/6.1 file

format or ASCII file format. All copies

of objections and hearing requests in

electronic form must be identified by

the docket control number OPP–300612.

No Confidential Business Information

(CBI) should be submitted through email. Electronic copies of objections and

hearing requests on this rule may be

filed online at many Federal Depository

Libraries.

FOR FURTHER INFORMATION CONTACT: By

mail: Ann Sibold, Registration Division

(7505C), Office of Pesticide Programs,

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460.

Office location, telephone number, and

e-mail address: Crystal Mall #2, 1921

Jefferson Davis Hwy., Arlington, VA,

(703) 305–6788, e-mail:

sibold.ann@epa.gov.

SUPPLEMENTARY INFORMATION: In the

Federal Register of June 20, 1997 (62 FR

33641) (FRL–5723–7), EPA issued a

notice pursuant to section 408 of the

FFDCA, 21 U.S.C. 346a(e), announcing

the filing of a pesticide petition for a

tolerance (PP 7F4832) by Rhone Poulenc

AG, Inc., P.O. Box 12014, 2 T.W.

Alexander Drive, Research Triangle

Park, NC 27709. This notice included a

summary of the petition prepared by

Rhone Poulenc AG, Inc., the registrant.

There were 11 comments received in

response to the notice of filing and all

supported establishing the tolerance.

The petition proposed to use a 56%

flowable solid (FS) formulation (Product

name: ICON 6.2 FS Insecticide) to treat

rice seed to control the pests rice water

weevil and chinch bugs.

The petition further requested that 40

CFR 180.517 be amended by

establishing new tolerances for

combined residues of the insecticide

fipronil, its metabolites MB46136 and

MB45950, and its photodegradate

MB46513 in or on rice grain at 0.04

parts per million (ppm) and rice straw

at 0.10 ppm. Tolerances for residues of

fipronil (expressed as fipronil and its

metabolites MB45950 and MB46136) in

or on animal commodities have recently

been established (40 CFR 180.517(a)).

Fipronil is registered in the United

States for use on field corn, on golf

course and commercial turf, on pets,

and in roach and ant bait stations.

I. Risk Assessment and Statutory

Findings

New section 408(b)(2)(A)(i) of the

FFDCA allows EPA to establish a

tolerance (the legal limit for a pesticide

chemical residue in or on a food) only

if EPA determines that the tolerance is

‘‘safe.’’ Section 408(b)(2)(A)(ii) of the

FFDCA defines ‘‘safe’’ to mean that

‘‘there is a reasonable certainty that no

harm will result from aggregate

exposure to the pesticide chemical

residue, including all anticipated

dietary exposures and all other

exposures for which there is reliable

information.’’ This includes exposure

through drinking water and in

residential settings, but does not include

occupational exposure. Section

408(b)(2)(C) requires EPA to give special

consideration to exposure of infants and

children to the pesticide chemical

residue in establishing a tolerance and

to ‘‘ensure that there is a reasonable

certainty that no harm will result to

infants and children from aggregate
38484 Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations

exposure to the pesticide chemical

residue. . . .’’

EPA performs a number of analyses to

determine the risks from aggregate

exposure to pesticide residues. First,

EPA determines the toxicity of

pesticides based primarily on

toxicological studies using laboratory

animals. These studies address many

adverse health effects, including (but

not limited to) reproductive effects,

developmental toxicity, toxicity to the

nervous system, and carcinogenicity.

Second, EPA examines exposure to the

pesticide through the diet (e.g., food and

drinking water) and through exposures

that occur as a result of pesticide use in

residential settings.

A. Toxicity

1. Threshold and non-threshold

effects. For many animal studies, a dose

response relationship can be

determined, which provides a dose that

causes adverse effects (threshold effects)

and doses causing no-observed effects

(the ‘‘no-observed effect level’’ or

‘‘NOEL’’).

Once a study has been evaluated and

the observed effects have been

determined to be threshold effects, EPA

generally divides the NOEL from the

study with the lowest NOEL by an

uncertainty factor (usually 100 or more)

to determine the Reference Dose (RfD).

The RfD is a level at or below which

daily aggregate exposure over a lifetime

will not pose appreciable risks to

human health. An uncertainty factor

(sometimes called a ‘‘safety factor’’) of

100 is commonly used since it is

assumed that people may be up to 10

times more sensitive to pesticides than

the test animals, and that one person or

subgroup of the population (such as

infants and children) could be up to 10

times more sensitive to a pesticide than

another. In addition, EPA assesses the

potential risks to infants and children

based on the weight of the evidence of

the toxicology studies and determines

whether an additional uncertainty factor

is warranted. Thus, an aggregate daily

exposure to a pesticide residue at or

below the RfD (expressed as 100% or

less of the RfD) is generally considered

acceptable by EPA. EPA generally uses

the RfD to evaluate the chronic risks

posed by pesticide exposure. For

shorter-term risks, EPA uses a RfD

approach or calculates a margin of

exposure (MOE) by dividing the

estimated human exposure into the

NOEL from the appropriate animal

study. Commonly, EPA finds MOEs

lower than 100 to be unacceptable. This

100-fold MOE is based on the same

rationale as the 100-fold uncertainty

factor.

Lifetime feeding studies in two

species of laboratory animals are

conducted to screen pesticides for

cancer effects. When evidence of

increased cancer is noted in these

studies, the Agency conducts a weight

of the evidence review of all relevant

toxicological data including short-term

and mutagenicity studies and structure

activity relationship. Once a pesticide

has been classified as a potential-human

carcinogen, different types of risk

assessments (e.g., linear low-dose

extrapolations or MOE calculation based

on the appropriate NOEL) will be

carried out based on the nature of the

carcinogenic response and the Agency’s

knowledge of its mode of action.

2. Differences in toxic effect due to

exposure duration. The toxicological

effects of a pesticide can vary with

different exposure durations. EPA

considers the entire toxicity data base,

and based on the effects seen for

different durations and routes of

exposure, determines which risk

assessments should be done to assure

that the public is adequately protected

from any pesticide-exposure scenario.

Both short and long durations of

exposure are always considered.

Typically, risk assessments include

‘‘acute,’’ ‘‘short-term,’’ ‘‘intermediateterm,’’ and ‘‘chronic’’ risks. These

assessments are defined by the Agency

as follows.

Acute risk, by the Agency’s definition,

results from 1-day consumption of food

and water, and reflects toxicity which

could be expressed following a singleoral exposure to the pesticide residues.

High-end exposure to food and water

residues are typically assumed.

Short-term risk results from exposure

to the pesticide for a period of 1-7 days,

and therefore overlaps with the acute

risk assessment. Historically, this risk

assessment was intended to address

primarily dermal and inhalation

exposure which could result, for

example, from residential pesticide

applications. However, since enaction of

FQPA, this assessment has been

expanded to include both dietary and

non-dietary sources of exposure, and

will typically consider exposure from

food, water, and residential uses when

reliable data are available. In this

assessment, risks from average food and

water exposure, and high-end

residential exposure, are aggregated.

High-end exposures from all three

sources are not typically added because

of the very-low probability of this

occurring in most cases, and because the

other conservative assumptions built

into the assessment assure adequate

protection of public health. However,

for cases in which high-end exposure

can reasonably be expected from

multiple sources (e.g. frequent and

widespread homeowner use in a

specific geographical area), multiple

high-end risks will be aggregated and

presented as part of the comprehensive

risk assessment/characterization. Since

the toxicological endpoint considered in

this assessment reflects exposure over a

period of at least 7 days, an additional

degree of conservatism is built into the

assessment; i.e., the risk assessment

nominally covers 1-7 days exposure,

and the toxicological endpoint/NOEL is

selected to be adequate for at least 7

days of exposure. (Toxicity results at

lower levels when the dosing duration

is increased.)

Intermediate-term risk results from

exposure for 7 days to several months.

This assessment is handled in a manner

similar to the short-term risk

assessment.

Chronic risk assessment describes risk

which could result from several months

to a lifetime of exposure. For this

assessment, risks are aggregated

considering average exposure from all

sources for representative population

subgroups including infants and

children.

B. Aggregate Exposure.

In examining aggregate exposure,

section 408 of the FFDCA requires that

EPA take into account available and

reliable information concerning

exposure from the pesticide residue in

the food in question, residues in other

foods for which there are tolerances,

residues in groundwater or surface

water that is consumed as drinking

water, and other non-occupational

exposures through pesticide use in

gardens, lawns, or buildings (residential

and other indoor uses). Dietary exposure

to residues of a pesticide in a food

commodity are estimated by

multiplying the average daily

consumption of the food forms of that

commodity by the tolerance level or the

anticipated pesticide residue level. The

Theoretical Maximum Residue

Contribution (TMRC) is an estimate of

the level of residues consumed daily if

each food item contained pesticide

residues equal to the tolerance. In

evaluating food exposures, EPA takes

into account varying consumption

patterns of major identifiable subgroups

of consumers, including infants and

children. The TMRC is a ‘‘worst case’’

estimate since it is based on the

assumptions that food contains

pesticide residues at the tolerance level

and that 100% of the crop is treated by

pesticides that have established

tolerances. If the TMRC exceeds the RfD

or poses a lifetime cancer risk that is
Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38485

greater than approximately one in a

million, EPA attempts to derive a more

accurate exposure estimate for the

pesticide by evaluating additional types

of information (anticipated residue data

and/or percent of crop treated data)

which show, generally, that pesticide

residues in most foods when they are

eaten are well below established

tolerances.

II. Aggregate Risk Assessment and

Determination of Safety

The toxicology data base for fipronil

has previously been evaluated and was

considered adequate to support

registration for use on corn (62 FR

62970) (FRL–5757–4). Since that time,

MB46513 has been identified. It appears

to have greater toxicity than the parent,

fipronil. MB46513 is not an animal or

plant metabolite. Rather, it forms when

the parent compound fipronil is

exposed to sunlight. It is not present on

corn, but is potentially present on rice

due to the foliar application (to

germinated rice seed).

Consistent with section 408(b)(2)(D)

of the FFDCA, EPA has reviewed the

available scientific data and other

relevant information in support of this

action, EPA has sufficient data to assess

the hazards of fipronil and to make a

determination on aggregate exposure,

consistent with section 408(b)(2) of the

FFDCA, for tolerances for combined

residues of fipronil, its metabolites

MB46136 and MB45950, and its

photodegradate MB46513 in or on rice

grain at 0.04 ppm and rice straw at 0.10

ppm.

A. Toxicology Data Base

EPA has evaluated the available

toxicity data and considered its validity,

completeness, and reliability as well as

the relationship of the results of the

studies to human risk. EPA has also

considered available information

concerning the variability of the

sensitivities of major identifiable

subgroups of consumers, including

infants and children. The nature of the

toxic effects caused by fipronil and its

photodegradate MB46513 are discussed

in this unit.

1. Acute studies—i. Technical

fipronil. A battery of acceptable acute

toxicity studies place technical fipronil

in toxicity Categories II and III. It is

classified as a non-sensitizer.

ii. Icon 6.2 FS (56% fipronil). A

battery of acute toxicity studies

submitted for Icon 6.2 FS places it in

toxicity categories II and III. This

formulation is classified as a sensitizer.

iii. MB46513. Based on acute oral and

acute dermal studies, MB46513 is

classified in toxicity category I. No

studies were submitted for acute

inhalation, primary eye, primary

dermal, and dermal sensitization.

2. Subchronic toxicity testing. The

data base for subchronic toxicity is

considered complete. No additional

studies are required at this time.

i. Fipronil. a. An acceptable

subchronic oral toxicity feeding study in

the rat established the lowest observedeffect level (LOEL) to be 30 ppm for

males (1.93 milligram (mg)/kilogram

(kg)/day) and females (2.28 mg/kg/day)

based on alterations in serum-protein

values and increased weight of the liver

and thyroid. The NOEL was 5 ppm for

males (0.33 mg/kg/day) and females

(0.37 mg/kg/day).

b. An acceptable subchronic oral

toxicity feeding study in the mouse

established the LOEL at 25 ppm (3.2 and

4.53 mg/kg/day, for males and females,

respectively) based on a possible

decreased body-weight gain. The noobserved adverse-effect level (NOAEL)

was 10 ppm (1.27 and 1.72 mg/kg/day,

for males and females, respectively).

The NOEL is less than or equal to 1 ppm

(0.13 and 0.17 mg/kg/day for males and

females, respectively) based on hepatic

hypertrophy at all doses.

c. An acceptable subchronic oral

toxicity [capsule] study in the dog

established that the LOEL is 10.0 mg/kg/

day for males (based on clinical signs of

toxicity) and 2.0 mg/kg/day for females

(based on clinical signs of toxicity and

decreased body-weight gain). The NOEL

is 2.0 mg/kg/day for males and 0.5 mg/

kg/day for females.

d. An acceptable repeated dose

dermal study using the rat found that

the systemic LOEL was 10 mg/kg/day

based on decreased body-weight gain

and food consumption; the dermal

irritation LOEL is greater than 10.0 mg/

kg/day. The systemic NOEL was 5.0 mg/

kg/day; the dermal irritation NOEL was

greater than or equal to 10.0 mg/kg/day.

ii. MB46513. a. An acceptable

subchronic oral toxicity feeding study

using the rat found that the LOEL was

3 ppm (0.177 and 0.210 mg/kg/day for

males and females, respectively) based

on the occurrence of aggressivity,

irritability to touch and increased motor

activity in one male (these signs are also

observed in the mouse). The NOEL was

0.5 ppm (0.029 and 0.035 mg/kg/day for

males and females, respectively). The

study demonstrates that the metabolite

is more toxic than the parent chemical

fipronil when administered to rats for

90 days.

b. An acceptable subchronic oral

toxicity feeding study using the mouse

found that the LOEL is 2 ppm (0.32 mg/

kg/day), based on the aggressive and

irritable behavior with increased motor

activity in males. The NOEL is 0.5 ppm

(0.08 mg/kg/day).

c. An acceptable subchronic oral

toxicity feeding study using the dog

established that the LOEL is 35 ppm

(1.05 mg/kg/day), based on behavioral

changes in 2 out of 5 females. The NOEL

is 9.5 ppm (0.29 mg/kg/day).

3. Chronic toxicity studies. The data

base for chronic toxicity is considered

complete. No additional studies are

required at this time.

i. An acceptable chronic feeding study

in the rat using fipronil found that the

LOEL is 1.5 ppm for males (0.059 mg/

kg/day) and females (0.078 mg/kg/day)

based on an increased incidence of

clinical signs and alterations in clinical

chemistry and thyroid parameters. The

NOEL is 0.5 ppm for males (0.019 mg/

kg/day) and females (0.025 mg/kg/day).

The study demonstrated that fipronil is

carcinogenic to rats at doses of 300 ppm

in males (12.68 mg/kg/day) and females

(16.75 mg/kg/day).

ii. An acceptable chronic oral toxicity

[capsule] study in the dog using fipronil

established a LOEL at 2.0 mg/kg/day

based on clinical signs of neurotoxicity

and abnormal neurological

examinations. The NOEL is 0.2 mg/kg/

day.

4. Carcinogenicity studies. The data

base for carcinogenicity is considered

complete. No additional studies are

required at this time.

i. The results of a carcinogenicity

study in the rat using fipronil is

described in Unit II.A.3.i of this

preamble.

ii. A acceptable carcinogenicity

[feeding] study in the mouse using

fipronil found that the LOEL is 10 ppm

(1.181 mg/kg/day for males and 1.230

mg/kg/day for females) based on

decreased body-weight gain, decreased

food conversion efficiency (males),

increased liver weights and increased

incidence of hepatic histopathological

changes. The NOEL is 0.5 ppm (0.055

mg/kg/day for males and 0.063 mg/kg/

day for females). The study

demonstrated that fipronil is not

carcinogenic to CD–1 mice when

administered at doses of 30 ppm.

5. Developmental toxicity studies. The

data base for developmental toxicity is

considered complete. No additional

studies are required at this time.

i. Fipronil. a. An acceptable prenatal

developmental study in the rat found

that the maternal toxicity LOEL was 20

mg/kg/day based on reduced bodyweight gain, increased water

consumption, reduced food

consumption, and reduced food

efficiency. The maternal toxicity NOEL

was 4 mg/kg/day. The developmental

toxicity LOEL was greater than 20 mg/
38486 Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations

kg/day. Developmental toxicity NOEL

was 20 mg/kg/day or higher.

b. An acceptable prenatal

developmental study in the rabbit found

that the maternal toxicity LOEL was 0.1

mg/kg/day or lower, based on reduced

body-weight gain, reduced food

consumption and efficiency. Maternal

toxicity NOEL was less than 0.1 mg/kg/

day. The developmental toxicity LOEL

was greater than 1.0 mg/kg/day. The

developmental toxicity NOEL was 1.0

mg/kg/day or higher.

ii. MB46513. An acceptable prenatal

developmental study using the rat found

that the maternal toxicity LOEL was 2.5

mg/kg/day and the NOEL was 1.0 mg/

kg/day based an increase in clinical

signs of toxicity (reduced body-weight

gain, food consumption and food

efficiency). The Developmental Toxicity

LOEL was 2.5 mg/kg/day and the NOEL

was 1.0 mg/kg/day based on the slight

increase in fetal and litter incidence of

reduced ossification of several bones.

6. Reproduction toxicity studies. The

data base for reproductive toxicity is

considered complete. No additional

studies are required at this time.

An acceptable two-generation

reproduction study in the rat using

fipronil concluded that the LOEL for

parental (systemic) toxicity was 30 ppm

(2.54 mg/kg/day for males and 2.74 mg/

kg/day for females) based on increased

weight of the thyroid glands and liver in

males and females; decreased weight of

the pituitary gland in females; and an

increased incidence of follicular

epithelial hypertrophy in the females.

The NOEL for parental (systemic)

toxicity was 3 ppm (0.25 mg/kg/day for

males and 0.27 mg/kg/day for females).

The LOEL for reproductive toxicity

was 300 ppm (26.03 mg/kg/day for

males and 28.40 mg/kg/day for females)

based on clinical signs of toxicity in the

F1 and F2 offspring; decreased litter size

in the F1 and F2 litters; decreased body

weights in the F1 and F2 litters; decrease

in the percentage of F1 parental animals

mating; reduction in fertility index in F1

parental animals; reduced postimplantation survival and offspring

postnatal survivability in the F2 litters;

and delay in physical development in

the F1 and F2 offspring. The NOEL for

reproductive toxicity was 30 ppm (2.54

mg/kg/day for males and 2.74 mg/kg/

day for females).

7. Neurotoxicity. The data base for

neurotoxicity is considered complete.

No additional studies are required at

this time.

i. Fipronil. a.An acceptable acute

neurotoxicity study in the rat concluded

the following: The NOEL was 0.5 mg/kg

for males and females. The LOEL was

5.0 mg/kg for males and females based

on decreased hind-leg splay at the 7

hour post-treatment evaluation in males

and females.

b. An acceptable acute neurotoxicity

study in the rat concluded that the

NOEL was 2.5 mg/kg. The LOEL is 7.5

mg/kg, based on decreased body-weight

gains, food consumption and feed

efficiency in females, decreased

hindlimb splay in males (at 7-hours post

test) and decreased grooming in females

(14-days post test).

c. An acceptable subchronic

neurotoxicity screening battery in the

rat concluded the LOEL was 150 ppm

(8.89 mg/kg/day, males; 10.8 mg/kg/day,

females) based on the results of the

functional observational battery (FOB);

the NOEL was 5.0 ppm (0.301 mg/kg/

day, males; 0.351 mg/kg/day, females).

d. In a developmental neurotoxicity

study, fipronil was administered to 30

female rats/group in the diet at dose

levels of 0, 0.5, 10, or 200 ppm (0.05,

0.90, or 15 mg/kg/day, respectively)

from gestation day 6 to lactation day 10.

This study found that the maternal

LOEL was 200 ppm (15 mg/kg/day),

based on decreased body weight, bodyweight gain, and food consumption. The

maternal NOEL was 10 ppm (0.90 mg/

kg/day). The developmental toxicity

LOEL is 10 ppm (0.9 mg/kg/day), based

on a marginal but statistically

significant decrease in group mean pup

weights during lactation and significant

increase in time of preputial separation

in males. The NOEL for developmental

toxicity is 0.5 ppm (0.05 mg/kg/day).

The developmental neurotoxicity LOEL

is 200 ppm (15 mg/kg/day) based on:

Decreased auditory startle response;

reduced swimming direction scores,

group mean angle measurements, and

water ‘‘Y’’ maze times trails; and

decreased absolute-brain weights. The

NOEL for developmental neurotoxicity

is 10 ppm (0.90 mg/kg/day).

It is noted that developmental toxicity

occurred at a dose lower than the

maternal-toxicity NOEL in this study.

However, EPA did not consider this to

indicate increased susceptibility to

infants and children. See Unit II.F.1.ii.d

of this preamble for a detailed

discussion of this point.

ii. MB46513. An acceptable acute

neurotoxicity study in the rat concluded

that the neurobehavioral LOEL for rats

is 12 mg/kg based on decreases in bodyweight gains and food consumption for

males and females during the week

following treatment, significant

decreases in locomotor activity 6-hours

post dosing for both males and females,

decreases in hind-limb splay and rectal

temperature at 6-hours post dose in

males and females, decreases in the

proportion of high-dose males with an

immediate righting reflex on days 7 and

14. Decreased forelimb grip strength in

males on day 7 and increased forelimb

grip strength in high-dose females at 6-

hours post dosing was possibly related

to the treatment, because there were also

slight increases in forelimb grip strength

in high-dose males at 6 hours and slight

decreases in forelimb grip strength in

high dose females at 7 days and in highdose males and females at 14 days.. The

NOEL is 2 mg/kg.

8. Mutagenicity. The available studies

indicate that fipronil and MB46513 are

not mutagenic in bacteria and are not

clastogenic in vitro or in vivo up to

doses that showed clear test material

interaction with the target cells. Based

on these considerations, EPA concluded

that there is no concern for

mutagenicity. The submitted test battery

for both compounds satisfy the new

mutagenicity initial testing battery

guidelines. No further studies are

required at this time.

i. Fipronil. a. An acceptable gene

mutation/bacteria test using salmonella

typhimurium concluded that fipronil

was not mutagenic.

b. An acceptable in vitro gene

mutation assay in mammalian cells/

Chinese hamster V79 cells concluded as

follows: Fipronil was negative for

inducing forward gene mutations at the

HGPRT locus in cultured Chinese

hamster V79 cells.

c. An acceptable cytogenetic in vivo

micronucleus assay in the mouse

concluded as follows: There was no

evidence of a clastogenic or aneugenic

effect at any dose or at any harvest time.

d. An acceptable cytogenetic assay in

human lymphocytes concluded as

follows: There was no evidence of a

clastogenic effect when human

lymphocytes were exposed in vitro to

fipronil.

ii. MB46513. a. An acceptable gene

mutation/bacteria test using salmonella

typhimurium showed that there was no

evidence of a mutagenic response at any

dose.

b. An acceptable gene mutation/in

vitro assay in mammalian cells

considering the HPRT locus in Chinese

Hamster Ovary (CHO) cells showed that

MB46513 did not induce forward

mutations at the HPRT locus in CHO

cells at any dose level tested.

c. An acceptable cytogenetics/in vivo

mouse bone marrow micronucleus assay

showed that there was no significant

increase in the frequency of MPCEs in

bone marrow after any MB46513

treatment time; therefore, the test article

is considered negative in this

micronucleus assay.

9. Metabolism study. The data base for

metabolism is considered to be
Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38487

complete. No additional studies are

required at this time.

i. Fipronil. An acceptable metabolism

study in the rat using 14–C labeled and

unlabeled fipronil showed the

following: With oral dosing, the rate and

extent of absorption appeared similar

among all dose groups, but may have

been decreased at the high dose. There

were no significant sex-related

differences in excretion. Feces appeared

to be the major route of excretion for

fipronil derived radioactivity, where

45–75% of an administered dose was

excreted. Excretion in urine was

between 5–25%. Major metabolites in

urine included two ring-opened

products of the metabolite MB45897,

two oxidation products (MB46136 and

RPA200766), and the parent chemical.

In feces, the parent was detected as a

significant fraction of the sample

radioactivity as well as the oxidation

product MB46136 and MB45950. Since

MB46513 is not an animal metabolite

but a photodegradate, it was not found

in this study.

ii. MB46513. In a acceptable rat

metabolism study, 14C labeled MB46513

was administered to rats by gavage as a

single dose or as a single dose following

a 14–day pretreatment with unlabeled

MB46513. Unchanged MB46513 in

urine accounted for less than 0.1% of

the dose. Fecal excretion of unchanged

MB46513 is the principal pathway for

elimination of MB46513 from rats. The

high levels of radioactivity in fat

compared to blood and the prolonged

elimination half-life indicate that there

is a potential for bioaccumulation of

MB46513 in fatty tissues.

10. Dermal absorption—i. Fipronil.

An acceptable study using the rat found

that the quantity of fipronil absorbed

was less than 1% at all doses. The

system was saturated at 3.88 mg/cm2.

The dermal absorption rat was

calculated to be less than 1% at 24

hours.

ii. MB46513. An acceptable study in

the rat using [14C] labeled MB46513

found that after 24 hours of exposure,

dermal absorption of MB46513 was

minimal. For all dose groups, the

majority of the dose was not absorbed

(90.2–102.3%), and only trace amounts

(equal to or less than 0.1%) of

radioactivity were excreted in the urine

and feces. There was 2.35% adhered to

the skin and absorbed at the 10 hour

time point with the lowest dose applied

(0.006 mg/cm2).

11. Special studies—i. Fipronil. a. A

supplemental thyroid function study in

the rat showed the following: The

treatment with fipronil or Noxyflex

appeared to result in stimulation of the

thyroid glands as evidenced by

increased accumulation of 125I in the

thyroid glands and by increases in the

ratios of radioactive distribution

between the blood and thyroid. These

changes were accompanied by increases

in thyroid weight. Treatment with

propylthiouracil (PTU) produced

decreases in the amount of 125I

incorporated in the thyroid and in the

blood: Thyroid ratios along with

elevated levels of 125I in the blood.

However, the weights of the thyroids

from these animals were increased by

over 2.5 fold compared to the controls

and therefore, the ratio of 125I in the

blood to thyroid weight was reduced.

The administration of perchlorate

produced further reductions in the 125I

content in the thyroids and in the blood:

Thyroid 125I radioactivity ratio. There

was no evidence of an inhibition of

iodide incorporation by either fipronil

or noxyflex.

b. A supplemental thyroxine

clearance study in the rat using

technical fipronil showed the following:

Fipronil had no effect on mortality or

other ante mortem parameters.

Phenobarbital-treated animals were

observed to have collapsed posture,

lethargy and shallow breathing on the

first day of treatment. There was no

effect of fipronil on clearance after 1 day

of treatment. However, after 14 days,

there was a decrease in terminal half life

(52% of control level) and increases in

clearance and volume of distribution

(261% and 137% of control level,

respectively). The effects seen with

phenobarbital treatment were similar,

although quantitatively not as severe

and were evident on day one of

treatment.

c. An acceptable 28–day dietary study

in the rat concluded that the LOEL is 25

ppm or lower (3.4 mg/kg/day in males;

3.5 mg/kg/day in females), based on

clinical laboratory changes, increased

absolute liver weights in females and

histopathological alterations in the

thyroid glands. The NOEL is less than

25 ppm.

ii. MB46513. An acceptable 28–day

dietary range-finding study in the rat

measured thyroid hormone levels as

well as standard study parameters. It

found that the LOEL is 30 ppm (2.20

and 2.32 mg/kg/day for males and

females, respectively), based on clinical

signs including piloerection, curling up

and thin appearance; and decreased

body weights in both sexes. The NOEL

is 3 ppm (0.23 and 0.24 mg/kg/day for

males and females, respectively).

B. Toxicology Endpoints

The toxicology endpoints for fipronil

and MB46513 are presented in this unit.

1. Fipronil—i. RfD. The RfD for

fipronil is 0.0002 mg/kg/day using a

NOEL of 0.019 mg/kg/day (0.5 ppm)

established from a combined chronic

toxicity/carcinogenicity study in rats

and an uncertainty factor of 100. The

LOEL=1.5 ppm (male (M): 0.059 mg/kg/

day; female (F): 0.078 mg/kg/day), based

on an increased incidence of clinical

signs (seizures and death) and

alterations in clinical chemistry

(protein) and thyroid parameters.

ii. Carcinogenic classification and risk

quantification. EPA has classified this

chemical as a Group C—Possible

Human Carcinogen, based on increases

in thyroid follicular-cell tumors in both

sexes of the rat, which were statistically

significant by both pair-wise and trend

analyses. EPA has used the RfD

methodology to estimate human risk

because the thyroid tumors are due to a

disruption in the thyroid-pituitary

status. There was no apparent concern

for mutagenicity.

iii. Dermal absorption. The percent

absorbed was less than 1% at 24 hours

based on a dermal absorption study.

iv. Other toxicological endpoints—a.

Acute dietary (1 day). In an acute

neurotoxicity study in rats the NOEL

was 2.5 mg/kg/day based on decreased

body-weight gains, food consumption

and feed efficiency in females, and

decreased hind-limb splay in males at 7-

hours post dosing at 7.5 mg/kg/day

LOEL. Although a developmental

neurotoxicity study with the parent

compound fipronil had a lower NOEL,

EPA determined that the effects from

that study are not attributable to a single

exposure (dose) and therefore are not

appropriate for acute dietary-risk

assessments.

b. Short- and intermediate-term

residential (dermal). In a 21-day dermal

study the NOEL was 5 mg/kg/day based

on decreased body-weight gain and food

consumption in male and female rabbits

observed at the LOEL of 10 mg/kg/day.

The dermal NOEL is supported by the

oral NOEL of 0.05 mg/kg/day

established in a developmental

neurotoxicity study when used in

conjunction with a dermal absorption

factor of 1%. This yields an equivalentdermal dose of 5 mg/kg/day.

c. Chronic residential (non-cancer). In

a combined chronic toxicity/

carcinogenicity study in the rat, the

NOEL is 0.5 ppm (M: 0.019 mg/kg/day;

F: 0.025 mg/kg/day), based on an

increased incidence of clinical signs

(seizures and death) and alterations in

clinical chemistry (protein) and thyroid

parameters (increased TSH, decreased

T4) at 1.5 ppm (M: 0.059 mg/kg/day; F:

0.078 mg/kg/day). Since the NOEL

identified is from an oral study, a
38488 Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations

dermal absorption factor of less than 1%

was used in risk calculations. (This

study/dose was also used to establish

the chronic RfD).

2. MB46513—i. RfD. There is no longterm (chronic or carcinogenicity) studies

are available for MB46513. However, the

toxicity profile of MB46513 indicate this

material to be approximately 10 times

more potent than the parent compound

when the NOELs/LOELs are compared

(with the exception of the acute toxicity

tests). See table 1 in this preamble.

TABLE 1.—A COMPARISON OF

TOXICITIES OF PHOTODEGRADATE

MB46513 AND FIPRONIL

Study Photodegradate

MB46513 Fipronil

Acute

Oral.

LD50= 16 mg/kg LD50= 92 mg/

kg

Acute

Neurotoxicity.

NOEL/LOEL= 2/

12 mg/kg

NOEL/LOEL=

2.5/7.5 mg/

kg

NOEL/LOEL=

0.5/5.0 mg/

kg

28–Day

Oral—

Rat.

NOEL/LOEL=

0.23/2.2 mg/

kg/day

NOEL/LOEL=

3.4 mg/kg/

day lowest

dose tested

(LDT)

90–Day

Oral—

Mouse.

NOEL/LOEL=

0.08/0.32 mg/

kg/day

NOEL/LOEL=

1.7/3.2 mg/

kg/day

90–Day

Oral—

Rat.

NOEL/LOEL=

0.029/0.18

mg/kg/day

NOEL= 0.33/

1.9 mg/kg/

day

Developmental—

Rat.

Maternal NOEL/

LOEL= 1/2.5

mg/kg/day

Developmental

NOEL/LOEL=

1/2.5 mg/kg/

day

Maternal

NOEL/

LOEL= 4/20

mg/kg/day

Developmental

NOEL/

LOEL= 20

mg/kg/day

highest dose

tested (HDT)

As shown in table 1 of this preamble,

the 28-day and 90-day subchronic oral

studies and oral developmental studies

consistently demonstrated an

approximately 10-fold greater potency

of MB46513 as compared to the parent

compound, fipronil. In the acute oral

tests, the difference between the LD50

values for MB46513 and fipronil is not

considered significant due to the

insensitivities inherent in this test.

EPA concluded that there is sufficient

experimental evidence to warrant the

application of a 10-fold Potency

Adjustment Factor (PAF) to the chronic

NOEL for the parent compound to

calculate a chronic NOEL for MB46513

in the absence of test data on the

chemical. An adjusted NOEL was

established at 0.0019 mg/kg/day for

MB46513.

An Uncertainty Factor (UF) of 100

was applied to account for inter (10 x)-

and intra-(10x) species variation.

ii. Carcinogenic classification and risk

quantification. No carcinogenicity

studies are available with MB46513.

Fipronil, the parent compound, was

classified as a Group C Carcinogen

(Possible Human Carcinogen). This

classification is based on increased

incidence of thyroid follicular-cell

tumors in rats. EPA used the RfD

methodology for the quantification of

human risk because the thyroid tumors

are related to a disruption in the

thyroid-pituitary status and there was

no apparent concern for mutagenicity or

available information from structurally

related analogs. EPA has no reason to

believe MB46513 is more carcinogenic

than the parent. EPA determined that it

was appropriate to use the RfD

methodology to quantify chronic risk for

MB46513. The NOEL used for the

chronic RfD has been adjusted by the

PAF to account for the fact that

MB46513 is about 10 times more toxic

than the parent (except for acute

toxicity).

iii. Dermal absorption. The percent

absorbed is estimated at approximately

2% at 10 hours based on a dermal

absorption study with MB46513.

iv. Other toxicological endpoints—a.

Acute dietary. The NOEL is 2 mg/kg in

an acute neurotoxicity study in rats

(with MB46513) based on significant

decreases in locomotor activity in both

sexes during the first 30 minutes as well

as decreases in hind-limb splay and

rectal temperature in both sexes at 6-

hours post dosing at 12 mg/kg/day

LOEL. Effects were seen on the day of

treatment after a single-oral exposure

(dose) and thus is appropriate for this

risk assessment. For reasons noted in

Unit II.B.1.iv of this preamble, EPA did

not use a developmental neurotoxicity

study with the parent compound

fipronil for this risk assessment.

b. Short- and intermediate-term

dermal exposure (1 to 7 days) (1 week

to several months). The adjusted dose of

0.5 mg/kg/day was derived by dividing

the study NOEL of 5 mg/kg/day by the

PAF of 10 (5/10= 0.5 mg/kg/day). The

LOEL was based on decreases in bodyweight gain and food consumption. The

dose and endpoint from the 21-day

dermal study with the parent compound

was used for the following reasons:

(1) A 21–dermal toxicity study with

MB46513 is not available.

(2) There is low potential for risk from

dermal exposure due to minimal dermal

absorption as indicated for both the

parent (< 1%) and the MB46513 (2%)

materials.

(3) The developmental/developmental

neurotoxicity NOEL of 0.05 mg/kg/day

for fipronil (established in the

developmental neurotoxicity study),

adjusted for 1% dermal absorption (DA),

results in a comparable dermal dose of

5 mg/kg/day (i.e., 0.05 mg/kg/day ′ 1%

DA= 5 mg/kg/day) which essentially is

the same as the NOEL for fipronil in the

21–day dermal toxicity study.

Residential exposure to MB46513 is

not expected while spraying or handling

a recently treated pet as these are brief

periods usually occurring indoors, and

MB46513 forms upon exposure to

sunlight. Post-application exposure to

the degradate is also not expected due

to the products reportedly strong

affinity to the sebum and epidermis of

pets.

c. Chronic dermal exposure (several

months to lifetime). Based on the

current use pattern for MB46513 (i.e., 1

application/year at planting), long-term

exposure via the dermal route is not

expected. Residential exposures are not

chronic in nature as label uses for pets

indicate treatment every 1 to 3 months.

d. Recommendation for aggregate

exposure risk assessments. An aggregate

systemic (oral) and dermal exposurerisk assessment is not appropriate due

to differences in the toxicity endpoints

observed between the oral

(neurotoxicity and alterations in clinical

chemistry and thyroid parameters) and

dermal (decreases in body-weight gain

and food consumption) routes. An

aggregate oral and inhalation risk

assessment is not required due to the

lack of exposure potential via the

inhalation route based on the current

use pattern.

C. Exposures and Risks

1. From food and feed uses.

Tolerances have been established (40

CFR 180.517) for the combined residues

of fipronil in or on on corn, eggs, meat,

milk, and poultry. Risk assessments

were conducted by EPA to assess

dietary exposures and risks from

fipronil and MB46513 as follows:

i. Acute dietary risk. An acute dietary

risk assessment is required for fipronil

and its metabolites and degradate. The

NOEL of 2.5 mg/kg was selected as the

endpoint to be used for fipronil,

MB46136, MB45950, and MB46513.

Since MB46513 does not appear to be

significantly more acutely toxic than the

parent, it was incorporated into the

acute dietary risk evaluation system

(DRES) run for rice. If further

refinements in the acute dietary risk

assessment are required in the future, a

separate DRES run for MB46513 only

will be performed.
Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38489

TABLE 2.—ACUTE RISK FOR FIPRONIL,

ITS METABOLITES, AND DEGRADATE

Subgroup

RfD

(mg/

kg/

day)

Level of

concern

Exposure

(mg/kg/

day)

Percent

of

RfD

General

U.S.

Population.

0.025 100%

RfD

0.0018 7

Infants (<

1 year).

0.025 100%

RfD

0.003 12

Children

(1–6

years).

0.025 100%

RfD

0.003 12

Females

(13+

years).

0.025 100%

RfD

0.0012 5

TABLE 2.—ACUTE RISK FOR FIPRONIL,

ITS METABOLITES, AND

DEGRADATE—Continued

Subgroup

RfD

(mg/

kg/

day)

Level of

concern

Exposure

(mg/kg/

day)

Percent

of

RfD

Males

(13+

years).

0.025 100%

RfD

0.0014 6

EPA does not consider the acute

dietary risks to exceed the level of

concern.

ii. Chronic dietary risk. A chronic

dietary risk assessment is required for

fipronil, MB46136, and MB45950. The

RfD used for the chronic dietary

analysis for parent fipronil and 2

metabolites is 0.0002 mg/kg/day. The

RfD used for MB46513 is 0.00002 mg/

kg/day. The analysis evaluates

individual food consumption as

reported by respondents in the United

States Department of Agriculture

(USDA) 1977–78 Nationwide Food

Consumption Survey (NFCS) and

accumulates exposure to the chemical

for each commodity.

Chronic DRES for fipronil, MB46136,

MB45950, and MB46513 are

summarized in Table 3 of this preamble.

The DRES analysis utilized the

anticipated residues calculated from

field-trial data for all animal, corn, and

rice commodities. The proposed fipronil

uses result in an Anticipated Residue

Contribution (ARC) that is equivalent to

the following percent of the RfD:

TABLE 3.—CHRONIC DIETARY RISK

Subgroups Fipronil, MB46136, and

MB45950 Photodegradate MB46513 Total

U.S. Population (48 states) ..................... 4.8% 1.7% 6.5%

Hispanics ................................................. 6.2% 2.9% 8.1%

Non-Hispanic Others ............................... 5.8% 3.9% 9.7%

Nursing Infants (< 1 year old) ................. 2.8% 2.3% 5.1%

Non-Nursing Infants (< 1 year old) .......... 11.2% 5.5% 16.7%

Females (13+ years, pregnant) ............... 3.3% 1.2% 4.5%

Females (13+ years, nursing) ................. 4.2% 1.6% 5.8%

Children (1–6 years old) .......................... 11.4% 3.8% 15.2%

Children (7–12 years old) ........................ 7.6% 2.3% 9.9%

Females (20+ years, not pregnant, not

nursing).

3.0% 1.2% 4.2%

EPA does not consider the chronic

dietary risk to exceed the level of

concern.

Anticipated residues. Section

408(b)(2)(E) of the FFDCA authorizes

EPA to consider available data and

information on the anticipated residue

levels of pesticide residues in food and

the actual levels of pesticide chemicals

that have been measured in food. If EPA

relies on such information, EPA must

require that data be provided 5 years

after the tolerance is established,

modified, or left in effect, demonstrating

that the levels in food are not above the

levels anticipated. Following the initial

data submission, EPA is authorized to

require similar data on a time frame it

deems appropriate.

Percent crop treated. Section

408(b)(2)(F) of the FFDCA states that the

Agency may use data on the actual

percent of food treated for assessing

chronic dietary risk onl if the Agency

can make the following findings:

(1) That the data used are reliable and

provide a valid basis to show what

percentage of the food derived from

such crop is likely to contain such

pesticide residue.

(2) That the exposure estimate does

not underestimate exposue for any

significant subpopulation group.

(3) If data are available on pesticide

use and food consumption in a

particular area, the exposure estimate

does not understate exposue for the

population in such area. In addition, the

Agency must provide for periodic

evaluation of any estimates used. To

provide for the periodic evaluation of

the estimate of percent crop treated as

required by the section 408 (b)(2)(F) of

the FFDCA, EPA may require registrants

to submit data on percent crop treated.

Anticipated residues, based on

average field trial values, and percent

crop treated information were used to

estimate dietary risk for the chronic

dietary risk assessment. For the acute

dietary risk assessment, anticipated

residues in blended commodities (such

as corn and rice processed commodities)

were used, without the adjustment for

percent crop treated. However, tolerance

level residues were used for fat; meat

by-products; meat of cattle, goats, hogs,

horses, sheep, and poultry; and eggs.

Since milk is a blended commodity, an

anticipated residue value was used. As

required by the FQPA, EPA will issue a

data call-in under section 408(f) of the

FFDCA to all fipronil registrants for data

on anticipated residues, to be submitted

no later than 5 years from the date of

issuance of these tolerances.

The percent of crop treated estimates

for fipronil and MB46513 were based on

an estimate of percent crop treated by

existing products used to control rice

water weevil and chinch bugs. In

addition, as set forth in 62 FR 62970,

market share estimates were used for

corn. They were based on an estimate of

percent crop treated by other

insecticides to control corn rootworm,

wireworm, and corn borer. EPA

considers these data reliable. A range of

estimates are supplied by this data and

the upper end of this range was used for

the exposure assessment. By using this

upper end estimate of percent crop

treated, the Agency is reasonably certain

that exposure is not underestimated for

any significant subpopulation. Further,

regional consumption information is

taken into account through EPA’s

computer-based model for evaluating

the exposure of significant

subpopulations including several

regional groups. Review of this regional
38490 Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations

data allows the Agency to be reasonably

certain that no regional population is

exposed to residue levels higher than

those estimated by the Agency.

To provide for the periodic evaluation

of these estimates of percent crop

treated and to meet the requirement for

data on anticipated residues, EPA may

require fipronil registrants to submit

data on percent crop treated.

2. Dietary exposure (drinking water

source). EPA does not have monitoring

data available to perform a quantitative

drinking water risk assessment for

fipronil at this time. Using

environmental fate data, EPA developed

ground and surface water exposure

estimates for use on corn and rice.

i. Ground water (tiered assessment).

The environmental fate data for fipronil

indicate a moderate to high persistence

and relatively low mobility in terrestrial

environments. Based on the SCI-GRO

model, acute drinking water

concentrations in shallow ground water

on highly vulnerable sites are not likely

to exceed the values set forth in tables

4–7 of this preamble:

TABLE 4.—ESTIMATED GROUND

WATER RESIDUES OF FIPRONIL AND

ITS METABOLITES

Corn parts per

billion (ppb) Rice (ppb)

Fipronil ..... 0.055 0.00804

MB46136 0.001 0.00038

MB45950 0.00036 0.000685

Total: 0.05636 0.009105

TABLE 5.—ESTIMATED GROUND

WATER RESIDUES OF

PHOTODEGRADATE MB46513

Corn

(ppb) Rice (ppb)

Photodegradate

MB46513.

0.00026 0.004138

Chronic concentrations are not

expected to be higher than acute values.

Highly vulnerable sites are those with

low-organic matter, coarse textured soils

(e.g., sands and loamy sands) and

shallow-ground water. The fate data for

fipronil and its degradates indicate a

higher potential mobility on coarsetextured soils (sand or loamy sands).

ii. Surface water (tiered assessment).

Based on the environmental fate

assessment, fipronil, MB46513,

MB46136, and MB45950 can potentially

move into surface waters. Since fipronil

is used as an in-furrow application on

field corn, the runoff potential of

fipronil residues is expected to be lower

than for unincorporated surface

application techniques. Since

photodegradation is a major route of

degradation for fipronil, its dissipation

is expected to be dependent on physical

components of the water (i.e. sediment

loading) which affect sunlight

penetration. The maximum fipronil

concentration for acute (peak

concentration) and chronic (56–day

average ) based on the Tier 1 GENEEC

surface water modeling is shown in the

table 6 of this preamble:

TABLE 6.—SURFACE WATER CONCENTRATIONS FOR FIPRONIL AND ITS METABOLITES BASED ON GENEEC MODELING

Corn Rice

Acute Peak Estimated Environmental Concentration (EEC)

Chronic 56–day EEC Acute Peak EEC

(ppb)

Chronic 56–day EEC

(ppb)

Fipronil ..................................................................... 2.05 0.78 1.45 0.40

MB46136 .................................................................. 0.168 0.062 0.061 0.004

MB45950 .................................................................. 0.039 0.019 0.1296 0.013

Total .......................................................... 2.257 0.861 1.6406 0.417

TABLE 7.—SURFACE WATER CONCENTRATIONS FOR PHOTODEGRADATE MB46513 BASED ON GENEEC MODELING

Corn Rice

Acute Peak EEC Chronic 56–day EEC Acute Peak EEC

(ppb)

Chronic 56–day EEC

(ppb)

Photodegradate MB46513 ........................................ 0.014 0.009 0.359 0.066

iii. Drinking water risk (acute and

chronic). To calculate the Drinking

Water Level of Concern (DWLOC) for

acute exposure relative to an acute

toxicity endpoint, the acute dietary food

exposure (from the DRES analysis) was

subtracted from acute RfD to obtain the

acute exposure to fipronil (plus

MB45950 and MB46136) in drinking

water. To calculate the DWLOC for

chronic (non-cancer, cancer) exposure

relative to a chronic toxicity endpoint,

the chronic dietary food exposure (from

DRES) was subtracted from the chronic

RfD to obtain the acceptable chronic

(non-cancer) exposure to fipronil,

MB45950, and MB46136 in drinking

water. DWLOCs were then calculated

using default body weights and drinking

water consumption figures.

a. Acute risk. EPA has calculated

DWLOCs for acute exposure to fipronil,

MB45950, MB46136, and MB46513 in

surface and ground water for the U.S.

population and children (1–6 yrs ). They

are 810 and 220 ppb, respectively.

b. Chronic risk. For chronic (noncancer) exposure to fipronil (plus

MB45950 and MB46136) in surface and

ground water, the drinking water levels

of concern are 6.67 and 1.77 ppb for

U.S. population and children (1–6 years

old), respectively.

c. Maximum and Average

concentrations. Estimated maximum

concentrations of fipronil, MB45950,

MB46136, and MB46513 in surface and

ground water are 2.271 and 0.05662 ppb

(with 0.00026 ppb from MB46513

included), respectively. The estimated

average concentration of fipronil,

MB45950, and MB46136 in surface

water is 0.861 ppb. Chronic

concentrations in ground water are not

expected to be higher than the acute

concentrations. For the purposes of the

screening-level assessment, the

maximum and average concentrations in
Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38491

ground water are not believed to vary

significantly.

The maximum estimated

concentrations of fipronil, MB45950,

and MB46136 in surface and ground

water are less than EPA’s levels of

concern for fipronil, MB45950, and

MB46136 in drinking water as a

contribution to acute aggregate

exposure.

The estimated average concentrations

of fipronil, MB45950, and MB46136 in

surface and ground water are less than

EPA’s levels of concern for fipronil,

MB45950, and MB46136 in drinking

water as a contribution to chronic

aggregate exposure. Therefore, taking

into account the present uses and uses

proposed in this action, EPA concludes

with reasonable certainty that residues

of fipronil, MB45950, and MB46136 in

drinking water (when considered along

with other sources of exposure for

which EPA has reliable data) would not

result in unacceptable levels of

aggregate human health risk at this time.

d. MB46513 (chronic only). For

chronic (non-cancer) exposure to

MB46513 in surface and ground water,

the drinking water levels of concern are

0.69 and 0.19 ppb for U.S. population,

children (non-nursing infants, < 1 year

old), respectively. To calculate the

DWLOC for chronic (non-cancer,

cancer) exposure relative to a chronic

toxicity endpoint, the chronic dietary

food exposure (from DRES) was

subtracted from the RfD to obtain the

acceptable chronic (non-cancer)

exposure to MB46513 in drinking water.

DWLOCs were then calculated using

default body weights and drinking water

consumption figures.

Estimated maximum concentrations

of MB46513 in ground water is 0.00026

ppb. The estimated average

concentration of MB46513 in surface

water is 0.009 ppb. Chronic

concentrations in ground water are not

expected to be higher than the acute

concentrations. For the purposes of the

screening-level assessment, the

maximum and average concentrations in

ground water are not believed to vary

significantly. The estimated average

concentrations of MB46513 in surface

and ground water are less than EPA’s

levels of concern for MB46513 in

drinking water as a contribution to

chronic aggregate exposure. Therefore,

taking into account the present uses and

uses proposed in this action, EPA

concludes with reasonable certainty that

residues of MB46513 in drinking water

(when considered along with other

sources of exposure for which EPA has

reliable data) would not result in

unacceptable levels of aggregate human

health risk at this time.

3. From non-dietary exposure. The

residential uses of fipronil include the

use of ant and cockroach bait traps

ranging from 0.01 to 0.05 percent active

ingredient. In addition, three fipronil

products are registered to control fleas

and ticks on dogs and cats. These

products are applied to the fur of the

animal as a ready-to-use pump spray or

as a ready-to-use, pour-on, spot

treatment made along the back of the

animal between the shoulder blades.

i. Ant and roach baits. Exposure from

the use of fipronil in self contained bait

stations is expected to result in low

exposures since there is no contact with

the pesticide.

ii. Pet care. For purposes of setting a

tolerance, an aggregate short-term and

intermediate-term systemic (oral) and

dermal exposure risk assessment which

includes the pet care products is not

appropriate due to differences in the

toxicity endpoints observed between the

oral (neurotoxicity and alterations in

clinical chemistry and thyroid

parameters) and dermal (decreases in

body-weight gain and food

consumption) routes. Further, though

fipronil is currently registered for

residential uses, no chronic residential

exposure is anticipated.

4. Cumulative exposure to substances

with common mechanism of toxicity.

Fipronil is structurally similar to other

members of the pyrazole class of

pesticides (i.e., tebufenpyrad,

pyrazolynate, benzofenap, etc.). Further,

other pesticides may have common

toxicity endpoints with fipronil.

Section 408(b)(2)(D)(v) of the FFDCA

requires that, when considering whether

to establish, modify, or revoke a

tolerance, the Agency consider

‘‘available information’’ concerning the

cumulative effects of a particular

pesticide’s residues and ‘‘other

substances that have a common

mechanism of toxicity.’’ The Agency

believes that ‘‘available information’’ in

this context might include not only

toxicity, chemistry, and exposure data,

but also scientific policies and

methodologies for understanding

common mechanisms of toxicity and

conducting cumulative risk

assessments. For most pesticides,

although the Agency has some

information in its files that may turn out

to be helpful in eventually determining

whether a pesticide shares a common

mechanism of toxicity with any other

substances, EPA does not at this time

have the methodologies to resolve the

complex scientific issues concerning

common mechanism of toxicity in a

meaningful way. EPA has begun a pilot

process to study this issue further

through the examination of particular

classes of pesticides. The Agency hopes

that the results of this pilot process will

increase the Agency’s scientific

understanding of this question such that

EPA will be able to develop and apply

scientific principles for better

determining which chemicals have a

common mechanism of toxicity and

evaluating the cumulative effects of

such chemicals. The Agency anticipates,

however, that even as its understanding

of the science of common mechanisms

increases, decisions on specific classes

of chemicals will be heavily dependent

on chemical specific data, much of

which may not be presently available.

Although at present the Agency does

not know how to apply the information

in its files concerning common

mechanism issues to most risk

assessments, there are pesticides as to

which the common mechanism issues

can be resolved. These pesticides

include pesticides that are

toxicologically dissimilar to existing

chemical substances (in which case the

Agency can conclude that it is unlikely

that a pesticide shares a common

mechanism of activity with other

substances) and pesticides that produce

a common toxic metabolite (in which

case common mechanism of activity

will be assumed).

EPA does not have, at this time,

available data to determine whether

fipronil has a common mechanism of

toxicity with other substances or how to

include this pesticide in a cumulative

risk assessment. Unlike other pesticides

for which EPA has followed a

cumulative risk approach based on a

common mechanism of toxicity, fipronil

does not appear to produce a toxic

metabolite produced by other

substances. For the purposes of this

tolerance action, therefore, EPA has not

assumed that fipronil has a common

mechanism of toxicity with other

substances.

5. Endocrine disruption. EPA is

required to develop a screening program

to determine whether certain substances

(including all pesticides and inerts)

‘‘may have an effect in humans that is

similar to an effect produced by a

naturally occurring estrogen, or such

other endocrine effect...’’. The Agency is

currently working with interested

stakeholders, including other

government agencies, public interest

groups, industry, and research scientists

in developing a screening and testing

program and a priority setting scheme to

implement this program. Congress has

allowed 3 years from the passage of

FQPA (August 3, 1999) to implement

this program. At that time, EPA may

require further testing of this active
38492 Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations

ingredient and end use products for

endocrine disrupter effects.

D. Aggregate Risks and Determination of

Safety for U.S. Population

1. Acute aggregate exposure and risk.

Using refined exposure assumptions

(anticipated residues for blended

commodities), a high-end exposure

estimate (food only) was calculated for

these subgroups: females 13+ years, for

the general U.S. population, infants (< 1

year), children (1–6 years), and males

13+. These risk estimates are the same

as those displayed in table 2 of this

preamble.

The maximum estimated

concentrations of fipronil in surface and

ground water are less than EPA’s levels

of concern for fipronil in drinking water

as a contribution to acute aggregate

exposure.

2. Short- and intermediate-term

aggregate exposure and risk. An

aggregate systemic (oral) and dermal

exposure risk assessment is not

appropriate due to differences in the

toxicity endpoints observed between the

oral (neurotoxicity and alterations in

clinical chemistry and thyroid

parameters) and dermal (decreases in

body-weight gain and food

consumption) routes.

3. Chronic aggregate exposure and

risk. Chronic dietary exposure estimates

for fipronil, MB46136, MB45950, and

MB46513 utilized anticipated residues

and a projected market share and are

thus highly refined. For the U.S.

population, 6.5% of the RfD is occupied

by dietary (food) exposure. Though

fipronil is currently registered for

residential uses, no chronic residential

exposure is anticipated. The estimated

average concentrations of fipronil in

surface and ground water are less than

EPA’s levels of concern for fipronil in

drinking water as a contribution to

chronic aggregate exposure.

4. Aggregate cancer risk for U.S.

population. For fipronil plus MB46136

and MB45950, EPA finds that the

dietary risk concerns due to long-term

consumption of fipronil residues are

adequately addressed by the DRES

chronic exposure analysis using the

RfD. For MB46513, EPA finds that the

dietary risk concerns due to long-term

consumption of MB46513 residues are

adequately addressed by the DRES

chronic exposure analysis using the

RfD.

5. Safety finding. Based on Unit II.C.

of this preamble, EPA concludes that

there is a reasonable certainty of no

harm from aggregate exposure to

fipronil.

F. Aggregate Risks and Determination of

Safety for Infants and Children

1. Safety factor for infants and

children—i. In general. In assessing the

potential for additional sensitivity of

infants and children to residues of

fipronil, EPA considered data from

developmental toxicity studies in the rat

and rabbit, a two-generation

reproduction study in the rat, and a

developmental neurotoxicity study in

the rat. The developmental toxicity

studies are designed to evaluate adverse

effects on the developing organism

resulting from pesticide exposure

during prenatal development to one or

both parents. Reproduction studies

provide information relating to effects

from exposure to the pesticide on the

reproductive capability of mating

animals and data on systemic toxicity.

Growth, survival and general toxicity

are evaluated for two generations of

offspring. Developmental Neurotoxicity

studies are designed to evaluate adverse

effects on the nervous system of the

developing organism resulting from

pesticide exposure of the pregnant and

nursing mother during several critical

stages of prenatal and postnatal

development.

Section 408 of the FFDCA provides

that EPA shall apply an additional 10-

fold margin of safety for infants and

children in the case of threshold effects

to account for pre-and post-natal

toxicity and the completeness of the

database unless EPA determines that a

different margin of safety will be safe for

infants and children. Margins of safety

are incorporated into EPA risk

assessments either directly through use

of a MOE analysis or through using

uncertainty (safety) factors in

calculating a dose level that poses no

appreciable risk to humans. EPA

believes that reliable data support using

the standard MOE and uncertainty

factor (usually 100 for combined interand intra-species variability)) and not

the additional tenfold MOE/uncertainty

factor when EPA has a complete data

base under existing guidelines and

when the severity of the effect in infants

or children or the potency or unusual

toxic properties of a compound do not

raise concerns regarding the adequacy of

the standard MOE/safety factor.

ii. Data on Susceptibility—a.

Neurotoxicity. Fipronil has

demonstrated neurotoxicity in the acute

and subchronic rat neurotoxicity studies

as well as in the rat chronic/

oncogenicity and chronic dog studies.

b. Developmental toxicity. There are

acceptable rat and rabbit developmental

toxicity studies with fipronil. There is

no evidence of developmental toxicity

in either study. EPA also considered a

developmental study conducted for

MB46513. In that study, pregnant rats

received oral administration of

MB46513 (99.2%). For maternal

toxicity, the NOEL was 1.0 mg/kg/day

and the LOEL was 2.5 mg/kg/day based

on an increase in clinical signs of

toxicity (hair loss) and on reduced bodyweight gain, food consumption, and

food efficiency. For developmental

toxicity, the NOEL was 1.0 mg/kg/day

and the LOEL was 2.5 mg/kg/day based

on a slight increase in fetal and litter

incidence of reduced ossification of

several bones (hyoid, 5th/6th sternebrae,

1st thoracic vertebral body, pubic bone,

and one or two metatarsi). Most of the

reduced ossification is weak evidence of

a developmental effect. Although the

minor decrement in fetal weight at 2.5

mg/kg/day has questionable biological

relevance, the decrement is supported

by the delayed ossification.

c. Reproductive toxicity. There is an

acceptable two-generation reproduction

study in the rat with fipronil. Toxicity

to the offspring (clinical signs of

toxicity, decreased litter size, decreased

body weights, decreased pre- and

postnatal survival, and delays in

physical development.) occurred only at

levels where there was maternal toxicity

(including maternal mortality).

d. Developmental neurotoxicity. In an

acceptable study with fipronil,

developmental neurotoxicity

(behavioral changes and decreased

absolute brain weights) was seen only at

levels where there was maternal toxicity

(decreased body weight, body-weight

gain and food consumption). However,

developmental toxicity (including

marginal but statistically significant

decrease in group mean pup weights

during lactation, and significant

increase in time of preputial separation

in males) was seen at levels below levels

of maternal toxicity.

e. Adequacy of data. An acceptable

two-generation reproduction study in

rats and acceptable prenatal

developmental toxicity studies in rats

and rabbits have been submitted to the

Agency, meeting basic data

requirements, as defined for a food-use

chemical. In addition, an acceptable

developmental neurotoxicity study was

conducted with fipronil and reviewed

by the Agency. Further, EPA has a

developmental toxicity study for

MB46513. Where specific data on

MB46513 are not available, the toxicity

of the photodegradate can be reliably

estimated by comparing the fipronil and

MB46513 data bases and taking into

consideration the PAF. Therefore,

additional data on MB46513 are not

required at this time. There are no data
Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38493

gaps for the assessment of the effects of

fipronil on developing animals

following in utero and/or early postnatal

exposure.

f. Determination of susceptibility.

Although there is no evidence of

enhanced pre or post natal

susceptibility in infants and children in

the developmental and reproduction

studies for fipronil and MB46513, the

developmental neurotoxicity study for

fipronil identified a developmental

NOEL (0.05 mg/kg/day) which is less

than the maternal NOEL of 0.9 mg/kg/

day indicating an apparent

susceptibility issue. However, EPA

determined that the evidence regarding

susceptibility was not convincing due to

the equivocal nature of the findings. Of

principal importance were the following

conclusions:

(1) The effects observed in the

offspring at the LOEL of 0.9 mg/kg/day,

although statistically significant, were

marginal and appeared to define a

threshold response level for this study.

(2) The body weight findings of this

study are not supported by results of the

two-generation reproduction study in

rats at similar treatment levels.

EPA concluded that the apparent

increased susceptibility in the

developmental neurotoxicity study was

not supported by the overall weight-ofthe-evidence (including no evidence for

increased susceptibility in the

developmental and reproduction

studies) from the fipronil data base.

iii. Determination of the FQPA safety

factor. There is a complete toxicity data

base for fipronil and exposure data is

complete or is estimated based on data

that reasonably accounts for potential

exposures. Further, as discussed in Unit

II.F.1.f of this preamble, EPA has

concluded that the studies do not show

that there is an increased susceptibility

for developmental effects. Accordingly,

EPA believes reliable data are available

to remove the additional 10-fold safety

factor for the protection of infants and

children.

2. Acute risk. The total dietary (food

only) percents of the acute RfD for these

population subgroups females 13+

years, for the general U.S. population,

infants (< 1 year), children (1–6 years),

and males 13+ ranged from 6–12%. This

calculation was based on an acute

neurotoxicity study NOEL in rats of 2.5

mg/kg/day for fipronil and 2.0 mg/kg/

day for MB46513. Despite the potential

for exposure to fipronil in drinking

water, EPA does not expect the acute

aggregate exposure to exceed EPA’s

level of concern. The small percent of

the acute dietary RfD calculated for

females 13+ years old provides

assurance that there is a reasonable

certainty of no harm for both females

13+ years and the pre-natal

development of infants.

3. Chronic risk. EPA has concluded

that the percentage of the RfD that will

be utilized by chronic dietary (food

only) exposure to residues of fipronil

ranges from 5.1% for nursing infants

less than 1 year old, up to 16.7% for

non-nursing infants less than 1 year old.

Despite the potential for exposure to

fipronil in drinking water, EPA does not

expect the chronic aggregate exposure to

exceed 100% of the RfD. There are uses

of fipronil that result in residential

exposure, but is not expected to result

in chronic exposure. EPA concludes

that there is a reasonable certainty that

no harm will result to infants and

children from acute, short- and

intermediate-term, or chronic aggregate

exposure to fipronil residues. That data

call-in [will] require such data to be

submitted every 5 years as long as the

tolerances remain in force.

III. Other Considerations

A. Metabolism In Plants and Animals

1. Rhone Poulenc AG, Inc. has

submitted data from a study

investigating the metabolism of fipronil

in rice. The qualitative nature of the

residue in rice is adequately understood

based on this metabolism study.

Fipronil was detected in all rice

commodities. MB46513 was also

detected in all commodities. MB45950

and MB46136, among other metabolites,

were also identified. EPA determined

that the fipronil residues of concern for

the tolerance expression and dietary risk

assessment in plants animals are the

parent and its metabolites MB46136 and

MB45950 and photodegradate

MB46513. The Agency, therefore, has

determined that the residues of concern

for the proposed tolerances are fipronil,

MB45950, MB46136, and MB46513.

2. Residues in eggs, meat, milk, and

poultry. Rice bran, grain, hulls, and

straws are animal feed items.

i. Fipronil. The maximum theoretical

dietary burden of fipronil to beef and

dairy cattle, based on the required

tolerances of 0.04 ppm for rice and 0.10

ppm for rice straw, is 0.04 ppm. The

maximum theoretical dietary burden of

fipronil to poultry, based on the

proposed tolerances of 0.04 ppm for rice

and 0.10 ppm for rice straw, is 0.04

ppm. Acceptable cow and poultry

feeding studies were submitted and

reviewed in conjunction with the

pesticide petition for corn. Based on

these studies, the Agency has already

established appropriate tolerance levels

for fipronil residues in/on animal

commodities.

ii. MB46513. Based on low potential

for residues in eggs, meat, and milk,

EPA will not require animal feeding

studies to be conducted with MB46513.

B. Analytical Enforcement Methodology

1. Plants. In conjunction with the

cotton petition, gas chromatography/

electron capture detector (GC/ECD)

method EC–95–303 has been proposed

for enforcement of tolerances for

residues of fipronil and its metabolites

MB45950, MB46136, and

photodegradate MB46513, and

RPA200766 in/on plant commodities.

The GC methods used for the analyses

of samples collected from the rice crop

field trials and processing study analyze

for each compound separately and are

adequate for collection of residue data.

Adequate method validation and

concurrent method recovery have been

submitted for these methods. These

methods are similar to the GC method

proposed for cottonseed which has

undergone a successful pesticide

method validation (PMV). The registrant

has been notified that all directions

pertaining to RPA200766 should also be

removed as this metabolite has been

determined to not be of regulatory

concern.

2. Animals. A method for the

determination of residues of fipronil,

MB45950, and MB46136 in animal

commodities was previously reviewed

in conjunction with a petition for corn

and animal raw agricultural

commodities (RACs), and has

undergone a successful PMV.

3. Multiresidue methods. A report on

multiresidue testing of fipronil,

MB45950, and MB46136 has been

received and forwarded to the Food and

Drug Administration (FDA). Acceptable

recoveries of fipronil, MB45950, and

MB46136 were obtained in corn grain.

A report on multiresidue testing of

MB46513 has been received and

forwarded to FDA. Acceptable

recoveries of MB46513 were obtained in

corn forage and cottonseed.

C. Magnitude of Residues

1. Plants. The submitted data indicate

that the combined residues of fipronil,

MB45950, MB46136, and MB46513 will

not exceed the proposed tolerance for

rice straw (0.10 ppm), or the proposed

tolerance for rice grain (0.04 ppm) in/on

samples harvested at maturity following

either a preplant incorporated (PPI)

broadcast application of the 80% water

dispersable granular (WDG) formulation

or seed treatment with a 10% liquid

formulation at about 0.05 lb active

ingredient (ai)/acre (A) (1 x the

proposed maximum rate).
38494 Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations

Based on the highest residue value

obtained from samples harvested

following the proposed PPI or seed

treatments at the proposed maximum

use rate, the proposed tolerance level of

0.10 ppm for rice straw is appropriate.

No residues of fipronil or MB46136,

MB45950, or MB46513 were detected in

rice grain, so the proposed tolerance

level for rice grain at the combined

limits of quantitation for fipronil,

MB46136, MB45950, and MB46513

(0.04 ppm) is appropriate.

2. Processed food/feed. Rhone

Poulenc AG, Inc. submitted data

depicting the potential for concentration

of fipronil residues in the processed

commodities of rice. The submitted rice

processing data are adequate. The data

indicate that total residues of fipronil,

MB45950, MB46136, and MB46513, and

RPA200766 are less than the limit of

quantitation (LOQ) (0.01 ppm) in/on

rice grain harvested at maturity

following PPI broadcast application of

the 80% Because treatment at 5–6 x the

label application rate did not result in

quantifiable levels of fipronil residues of

concern in rice grain, all further

requirements for the processing study

are waived, and no tolerances are

required for the processed commodities

of rice. As a result of this use, residues

of fipronil are not expected to exceed

the proposed or existing tolerances.

D. International Residue Limits

There are no CODEX, Canadian, or

Mexican MRLs established for fipronil

in/on rice RACs. Therefore, no

compatibility problems exist.

E. Rotational Crop Restrictions

An acceptable confined rotational

crop study with grain, grain sorghum,

lettuce, radishes, and wheat was

submitted and reviewed in conjunction

with the corn petition.

The rotational crop restrictions

specified on the labels (1 month for

leafy vegetables, 5 months for root

crops, and 12 months for small grains

and all other crops) are supported by the

results of the confined rotational crop

study.

IV. Conclusion

Therefore, the tolerances established

at 40 CFR 180.517 are amended to

include combined residues of the

insecticide fipronil, MB46136,

MB45950, and MB46513 in or on rice

grain at 0.04 ppm and rice straw at 0.10

ppm.

V. Objections and Hearing Requests.

The new FFDCA section 408(g)

provides essentially the same process

for persons to ‘‘object’’ to a tolerance

regulation issued by EPA under new

section 408(e) and (l)(6) as was provided

in the old section 408 and in section

409. However, the period for filing

objections is 60 days, rather than 30

days. EPA currently has procedural

regulations which govern the

submission of objections and hearing

requests. These regulations will require

some modification to reflect the new

law. However, until those modifications

can be made, EPA will continue to use

those procedural regulations with

appropriate adjustments to reflect the

new law.

Any person may, by September 15,

1998, file written objections to any

aspect of this regulation and may also

request a hearing on those objections.

Objections and hearing requests must be

filed with the Hearing Clerk, at the

address given above (40 CFR 178.20). A

copy of the objections and/or hearing

requests filed with the Hearing Clerk

should be submitted to the OPP docket

for this rulemaking. The objections

submitted must specify the provisions

of the regulation deemed objectionable

and the grounds for the objections (40

CFR 178.25). Each objection must be

accompanied by the fee prescribed by

40 CFR 180.33. If a hearing is requested,

the objections must include a statement

of the factual issues on which a hearing

is requested, the requestor’s contentions

on such issues, and a summary of any

evidence relied upon by the requestor

(40 CFR 178.27). A request for a hearing

will be granted if the Administrator

determines that the material submitted

shows the following: There is genuine

and substantial issue of fact; there is a

reasonable possibility that available

evidence identified by the requestor

would, if established, resolve one or

more of such issues in favor of the

requestor, taking into account

uncontested claims or facts to the

contrary; and resolution of the factual

issues in the manner sought by the

requestor would be adequate to justify

the action requested (40 CFR 178.32).

Information submitted in connection

with an objection or hearing request

may be claimed confidential by marking

any part or all of that information as

CBI. Information so marked will not be

disclosed except in accordance with

procedures set forth in 40 CFR part 2.

A copy of the information that does not

contain CBI must be submitted for

inclusion in the public record.

Information not marked confidential

may be disclosed publicly by EPA

without prior notice.

VI. Public Record

EPA has established a record for this

rulemaking under docket control

number OPP–300612 (including any

comments and data submitted

electronically). A public version of this

record, including printed, paper

versions of electronic comments, which

does not include any information

claimed as CBI, is available for

inspection from 8:30 a.m. to 4 p.m.,

Monday through Friday, excluding legal

holidays. The public record is located in

room 119 of the Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7502C), Office of Pesticide Programs,

Environmental Protection Agency,

Crystal Mall ι2, 1921 Jefferson Davis

Hwy., Arlington, VA.

Electronic comments may be sent

directly to EPA at:

opp-docket@epamail.epa.gov.

Electronic comments must be

submitted as an ASCII file avoiding the

use of special characters and any form

of encryption.

The official record for this

rulemaking, as well as the public

version, as described above will be kept

in paper form. Accordingly, EPA will

transfer any copies of objections and

hearing requests received electronically

into printed, paper form as they are

received and will place the paper copies

in the official rulemaking record which

will also include all comments

submitted directly in writing. The

official rulemaking record is the paper

record maintained at the Virginia

address in ADDRESSES at the beginning

of this document.

VII. Regulatory Assessment

Requirements

This final rule establishes tolerances

under FFDCA section 408(d) in

response to a petition submitted to the

Agency. The Office of Management and

Budget (OMB) has exempted these types

of actions from review under Executive

Order 12866, entitled Regulatory

Planning and Review (58 FR 51735,

October 4, 1993). This final rule does

not contain any information collections

subject to OMB approval under the

Paperwork Reduction Act (PRA), 44

U.S.C. 3501 et seq., or impose any

enforceable duty or contain any

unfunded mandate as described under

Title II of the Unfunded Mandates

Reform Act of 1995 (UMRA) (Pub. L.

104–4). Nor does it require any prior

consultation as specified by Executive

Order 12875, entitled Enhancing the

Intergovernmental Partnership (58 FR

58093, October 28, 1993), or special

considerations as required by Executive

Order 12898, entitled Federal Actions to

Address Environmental Justice in

Minority Populations and Low-Income

Populations (59 FR 7629, February 16,
Federal Register / Vol. 63, No. 137 / Friday, July 17, 1998 /Rules and Regulations 38495

1994), or require OMB review in

accordance with Executive Order 13045,

entitled Protection of Children from

Environmental Health Risks and Safety

Risks (62 FR 19885, April 23, 1997).

In addition, since these tolerances and

exemptions that are established on the

basis of a petition under FFDCA section

408(d), such as the tolerances in this

final rule, do not require the issuance of

a proposed rule, the requirements of the

Regulatory Flexibility Act (RFA) (5

U.S.C. 601 et seq.) do not apply.

Nevertheless, the Agency has previously

assessed whether establishing

tolerances, exemptions from tolerances,

raising tolerance levels or expanding

exemptions might adversely impact

small entities and concluded, as a

generic matter, that there is no adverse

economic impact. The factual basis for

the Agency’s generic certification for

tolerance actions published on May 4,

1981 (46 FR 24950) and was provided

to the Chief Counsel for Advocacy of the

Small Business Administration.

VIII. Submission to Congress and the

General Accounting Office

The Congressional Review Act, 5

U.S.C. 801 et seq., as added by the Small

Business Regulatory Enforcement

Fairness Act of 1996, generally provides

that before a rule may take effect, the

agency promulgating the rule must

submit a rule report, which includes a

copy of the rule, to each House of the

Congress and to the Comptroller General

of the United States. EPA will submit a

report containing this rule and other

required information to the U.S. Senate,

the U.S. House of Representatives, and

the Comptroller General of the United

States prior to publication of the rule in

the Federal Register. This rule is not a

‘‘major rule’’ as defined by 5 U.S.C.

804(2).

List of Subjects in 40 CFR Part 180

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: July 2, 1998.

Peter Caulkins,

Acting Director, Registration Division, Office

of Pesticide Programs.

Therefore, 40 CFR chapter I is

amended as follows:

PART 180—[AMENDED]

1. The authority citation for part 180

continues to read as follows:

Authority: 21 U.S.C. 346a and 371.

2. In § 180.517 by revising the

introductory text of paragraph (a) and

adding the following entries to the table

in paragraph (a) to read as follows:

§ 180.517 Fipronil; tolerances for residues.

(a) General. Therefore, tolerances are

established for combined residues of the

insecticide fipronil (5-amino-1-[2,6-

dichloro-4-(trifluoromethyl)phenyl]-4-

[(1R,S)-(trifluoromethyl)sulfinyl]-1Hpyrazole-3-carbonitrile) and its

metabolites 5-amino-1-[2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-

[(trifluoromethyl) sulfonyl]-1Hpyrazole-3-carbonitrile and 5-amino-1-

[2,6-dichloro-4-(trifluoromethyl)

phenyl]-4-[(trifluoromethyl)thio]-1Hpyrazole-3-carbonitrile and its

photodegradate 5-amino-1-(2,6-dichloro4-(trifluoromethyl)phenyl]-4-[(1R,S)-

(trifluoromethyl)]-1H-pyrazole-3-

carbonitrile in or on the following items

at the levels specified:

Commodity Parts per million (ppm)

* * * *

*

Rice grain ............................. 0.04

Rice straw ............................ 0.10

* * * * *

[FR Doc. 98–18987 Filed 7–16–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[OPP–300681; FRL–6016–7]

RIN 2070–AB78

Pseudomonas Fluorescens Strain

PRA-25; Temporary Exemption From

the Requirement of a Tolerance

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: This rule establishes a

temporary exemption from the

requirement of a tolerance for residues

of the microbial pest control agent

pseudomonas fluorescens strain PRA-25

on peas, snap beans, sweet corn,

supersweet corn when applied/used on

vegetable seeds in the planter box

immediately before planting to reduce

seed rot and damping-off disease cause

by Pythium spp. and root rot caused by

Aphanomyces euteiches. Good Bugs,

Inc. submitted a petition to EPA under

the Federal Food, Drug, and Cosmetic

Act (FFDCA) as amended by the Food

Quality Protection Act of 1996 (FQPA)

(Pub. L. 104-170) requesting the

temporary/time-limited tolerance. This

regulation eliminates the need to

establish a maximum permissible level

for residues of pseudomonas

fluorescens strain PRA-25. The

tolerance will expire on July 31, 2001.

DATES: This regulation is effective July

17, 1998. Objections and requests for

hearings must be received by EPA on or

before September 15, 1998.

ADDRESSES: Written objections and

hearing requests, identified by the

docket control number [OPP–300681],

must be submitted to: Hearing Clerk

(1900), Environmental Protection

Agency, Rm. M3708, 401 M St., SW.,

Washington, DC 20460. Fees

accompanying objections and hearing

requests shall be labeled ‘‘Tolerance

Petition Fees’’ and forwarded to: EPA

Headquarters Accounting Operations

Branch, OPP (Tolerance Fees) and

forwarded to: EPA Headquarters

Accounting Operations Branch, OPP

(Tolerance Fees), P.O. Box 360277M,

Pittsburgh, PA 15251. A copy of any

objections and hearing requests filed

with the Hearing Clerk identified by the

docket control number, [OPP-300681],

must also be submitted to: Public

Information and Records Integrity

Branch, Information Resources and

Services Division (7502C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

a copy of objections and hearing

requests to Rm. 119, CM #2, 1921

Jefferson Davis Hwy., Arlington, VA.

A copy of objections and hearing

requests filed with the Hearing Clerk

may be submitted electronically by

sending electronic mail (e-mail) to: oppdocket@epamail.epa.gov. Copies of

electronic objections and hearing

requests must be submitted as an ASCII

file avoiding the use of special

characters and any form of encryption.

Copies of electronic objections and

hearing requests will also be accepted

on disks in WordPerfect 5.1/6.1 file

format or ASCII file format. All copies

of electronic objections and hearing

requests must be identified by the

docket number [OPP-300681]. No

Confidential Business Information (CBI)

should be submitted through e-mail.

Copies of electronic objections and

hearing requests on this rule may be

filed online at many Federal Depository

Libraries.

FOR FURTHER INFORMATION CONTACT: By

mail: Linda A. Hollis, c/o Product

Manager (PM) 90, Biopesticides and

Pollution Prevention Division (7511C),

Environmental Protection Agency, 401